Jun 14, 2003

Sympathetic innervation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease

The Journal of Pharmacology and Experimental Therapeutics
David S GoldsteinKrys Bankiewicz

Abstract

Cardiac sympathetic denervation occurs commonly in Parkinson's disease. This study explored whether analogous denervation occurs in primates with Parkinsonism from systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 6-[18F]Fluorodopamine positron emission tomographic scanning and plasma levels of catecholamines and their deaminated metabolites were used to assess sympathetic and adrenomedullary function in rhesus monkeys, in the untreated state (n = 3), 2 weeks after a series of four MPTP injections, before establishment of Parkinsonism (acute phase, n = 1); a month later, after four more MPTP doses, associated with severe Parkinsonism (subacute phase, n = 1); or more than 2 years from the last dose (remote phase, n = 3), with persistent severe Parkinsonism. A positive control received i.v. 6-hydroxydopamine 1 week before 6-[18F]fluorodopamine scanning. Acute MPTP treatment increased cardiac 6-[18F]fluorodopamine-derived radioactivity, whereas 6-hydroxydopamine markedly decreased cardiac radioactivity, despite similarly low plasma levels of catecholamines and metabolites after either treatment. Subacutely, plasma catecholamines remained decreased, but now with myocardial 6-[18F]fluorodopamine-derived...Continue Reading

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Citations

Mentioned in this Paper

MPTP-Induced Degeneration of the Striatum
Nonhuman primate
Catecholamine [EPC]
Sympathetic Nervous System
Muscle Innervation, Function
Catecholamines Measurement
Myocardium
Cercopithecidae
Platyrrhini
Parkinsonian Disorders

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